Immunocytochemical localization of DNA double-strand breaks in human and rat brains

Torres, Germán; Leheste, Joerg R.; Ramos, Raddy L.

doi:10.1016/j.neuroscience.2015.01.027

Cited by 7 publications

(6 citation statements)

References 22 publications

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“…Our findings related to the brain are reasonably consistent with previous studies (Suberbielle et al, 2013;Torres et al, 2015), in which a strong nuclear immunoreactivity was observed in the striatum (e.g., caudate/ putamen), hippocampus (e.g., dentate gyrus) and hypothalamus (e.g., anterior and paraventricular nucleus of the hypothalamus), areas of the brain with intricate circuitries related to motor activity, sequence learning and visceral function, respectively (Graybiel and Grafton, 2015). Together, the homogenous expression of DNA double-strand breaks at memory circuits support previous suggestions that transient increases in DNA doublestrand breaks in the dentate gyrus can spontaneously occur as a result of physiological activity (Suberbielle et al, 2013).…”

Section: Discussionsupporting

confidence: 93%

“…The subcellular distribution of 53BP1 immunoreactivity in these neural stem cells was entirely consistent with that documented for the ex vivo human and mouse brain material. Although we did not conduct double‐labeling studies to confirm whether neural stem cells are the only cells of the human brain to express the DNA damage signaling code, we did demonstrate in previous studies that only adult neurons but not oligodendrocytes or microglia are immunopositive for DNA double‐strand breaks (Torres et al, ).…”

Section: Resultsmentioning

confidence: 73%

“…The prevalence of endogenous DNA damage throughout the brain and peripheral nervous system raises the possibility that DNA double-strand breaks might also be core features of transient normal cell development and maintenance (Suberbielle et al, 2013). Indeed, human and mouse neurons as well as neural progenitors at different stages of development express high levels of DNA double-strand breaks which vary depending on physiological brain activity and brain regional organization (McKinnon, 2013;Rulten and Caldecott, 2013;Suberbielle et al, 2013;Torres et al, 2015). These differences in DNA strand-breaks may reflect the varied functional characteristic of DNA processing and repair that are available to nonreplicating or differentiated neurons.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, a well-characterized rabbit polyclonal antiserum was used for immunocytochemical localization of DNA double-strand breaks in human and mouse brains to expand our original findings of DNA damage signaling at the level of the cell nucleus (Torres et al, 2015). In addition, we surveyed the distribution pattern of DNA double-strand breaks in the mouse tongue, heart and testis to ascertain the degree of expression relative to that of the brain.…”

Section: Introductionmentioning

confidence: 99%

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Central and Peripheral Expression of DNA Double‐Strand Breaks in Human and Mouse Tissues

Castiglione

Ramos

Leheste

et al. 2018

The Anatomical Record

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Mammalian cells accumulate DNA lesions when they undergo phases of the cell cycle or during normal cellular activity. In this regard, several DNA repair signaling pathways have evolved to maintain genome stability and avoid the potential acquisition of mutations. To define and further characterize the expression of DNA double-strand breaks in humans and mice, we used immunocytochemistry to localize a DNA damage signal within the spatial confines of the cell nucleus. We show that DNA double-strand breaks are abundantly expressed in postmitotic neurons of the human and mouse brain. Notably, DNA double-strand breaks are present in human hypothalamic and mouse striatal and hippocampal cells, with stable expression of the nuclear signal detected throughout the mammalian brain. Analysis of the mouse tongue, heart, and testis shows that expression of DNA double-strand breaks is only demonstrated in circumscribed populations of peripheral cells. These data suggest that levels of DNA double-strand breaks are tissue-specific with the tongue, heart and testicular tissue having different thresholds of DNA repair and DNA damage from those outlined at the brain level. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Central and Peripheral Expression of DNA Double‐Strand Breaks in Human and Mouse Tissues

Castiglione

Ramos

Leheste

et al. 2018

The Anatomical Record

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“…To mark DSB, we first assessed expression of 53BP1, which is recruited specifically to DSB sites, where it forms foci ( Anderson et al., 2001 ; Suberbielle et al., 2013 ). Because of its critical role in the detection and repair of DSB in post-mitotic cells, 53BP1 displays a neuron-specific characteristic diffuse nuclear staining when assessed by immunofluorescence microscopy, whereas it forms bright fluorescent foci at DSB sites ( Suberbielle et al., 2013 ; Torres et al., 2015 ) ( Figures 1 B and S1 A). Importantly, this characteristic diffuse nuclear 53BP1 staining is absent in glia, which is useful to discriminate neurons from glia in a culture.…”

Section: Resultsmentioning

confidence: 99%

Borna disease virus docks on neuronal DNA double-strand breaks to replicate and dampens neuronal activity

et al. 2022

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Summary Borna disease viruses (BoDV) have recently emerged as zoonotic neurotropic pathogens. These persistent RNA viruses assemble nuclear replication centers (vSPOT) in close interaction with the host chromatin. However, the topology of this interaction and its consequences on neuronal function remain unexplored. In neurons, DNA double-strand breaks (DSB) have been identified as novel epigenetic mechanisms regulating neurotransmission and cognition. Activity-dependent DSB contribute critically to neuronal plasticity processes, which could be impaired upon infection. Here, we show that BoDV-1 infection, or the singled-out expression of viral Nucleoprotein and Phosphoprotein, increases neuronal DSB levels. Of interest, inducing DSB promoted the recruitment anew of vSPOT colocalized with DSB and increased viral RNA replication. BoDV-1 persistence decreased neuronal activity and response to stimulation by dampening the surface expression of glutamate receptors. Taken together, our results propose an original mechanistic cross talk between persistence of an RNA virus and neuronal function, through the control of DSB levels.

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Apoptotic Markers in the Midbrain of the Human Neonate After Perinatal Hypoxic/Ischemic Injury

Pagida

Konstantinidou

Chrysanthou‐Piterou

et al. 2019

Journal of Neuropathology &Amp; Experimental Neurology

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Our previous postmortem studies on neonates with neuropathological injury of perinatal hypoxia/ischemia (PHI) showed a dramatic reduction of tyrosine hydroxylase expression (dopamine synthesis enzyme) in substantia nigra (SN) neurons, with reduction of their cellular size. In order to investigate if the above observations represent an early stage of SN degeneration, we immunohistochemically studied the expression of cleaved caspase-3 (CCP3), apoptosis inducing factor (AIF), and DNA fragmentation by using terminal deoxynucleotidyltransferase-mediated dUTP-biotin 3′-end-labeling (TUNEL) technique in the SN of 22 autopsied neonates (corrected age ranging from 34 to 46.5 gestational weeks), in relation to the severity/duration of PHI injury, as estimated by neuropathological criteria. No CCP3-immunoreactive neurons and a limited number of apoptotic TUNEL-positive neurons with pyknotic characteristics were found in the SN. Nuclear AIF staining was revealed only in few SN neurons, indicating the presence of early signs of AIF-mediated degeneration. By contrast, motor neurons of the oculomotor nucleus showed higher cytoplasmic AIF expression and nuclear translocation, possibly attributed to the combined effect of developmental processes and increased oxidative stress induced by antemortem and postmortem factors. Our study indicates the activation of AIF, but not CCP3, in the SN and oculomotor nucleus of the human neonate in the developmentally critical perinatal period.

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Immunocytochemical localization of DNA double-strand breaks in human and rat brains

Cited by 7 publications

References 22 publications

Central and Peripheral Expression of DNA Double‐Strand Breaks in Human and Mouse Tissues

Central and Peripheral Expression of DNA Double‐Strand Breaks in Human and Mouse Tissues

Borna disease virus docks on neuronal DNA double-strand breaks to replicate and dampens neuronal activity

Apoptotic Markers in the Midbrain of the Human Neonate After Perinatal Hypoxic/Ischemic Injury

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